Research Highlights:

• GLP-1RA (glucagon-like peptide-1 receptor agonist) medications, which are prescribed to treat Type 2 diabetes and to help with weight loss, were found to reduce the number of deaths, amputations and hospitalizations among people with Type 2 diabetes and narrowed leg arteries associated with PAD (peripheral artery disease).
• People who had severely blocked arteries in their legs and those with obesity were most likely to benefit from taking a GLP-1RA.
• In addition, people taking GLP1-RAs needed fewer procedures to restore blood flow to their legs.

DALLAS - July 1, 2026 (NEWMEDIAWIRE) - GLP-1 receptor agonists (GLP-1 RA) medications were shown to reduce the number of deaths, amputations and hospitalizations among people with Type 2 diabetes who also had narrowed leg arteries associated with PAD (peripheral artery disease), according to new, independent research published today in the Journal of the American Heart Association, an open-access, peer-reviewed journal of the American Heart Association.

“Because GLP-1 RAs show significant benefits, especially for high-risk patients with severe circulation problems in their legs, clinicians should consider prescribing GLP-1s because peripheral artery disease, also known as PAD, has limited treatment options,” said study author Aravinda Nanjundappa, M.D., an interventional cardiologist in the invasive & interventional cardiology section in the Robert and Suzanne Tomisich Department of Cardiovascular Medicine at the Cleveland Clinic in Cleveland. “Our findings indicate these medications may improve long-term health for people with PAD, in addition to managing blood sugar and weight loss.”

In this study, researchers reviewed the health records for more than 2,000 adults with Type 2 diabetes and PAD to explore the potential benefits of GLP-1 RA medications. They found that the positive impact of GLP-1 RAs on overall health surpassed that of metformin, the most widely prescribed medication for people with Type 2 diabetes, in most categories.

Compared with people taking metformin, among those taking GLP-1 RAs, the analysis found:

• a 26% reduction in all causes of death;
• a 13% reduction in hospitalizations;
• up to a 48% reduction in amputations; and
• about 36% reduction in the need for procedures to open clogged arteries.
• However, the rate of heart attack, stroke and serious kidney events were similar between both groups.

Researchers noted that the link between GLP1-RAs and medical benefits was strongest among participants with severe PAD, including chronic limb-threatening ischemia and those with a body mass index of 30 or higher, which is considered obesity.

“Obesity and PAD, including chronic limb-threatening ischemia, are linked to increased inflammation, poor blood vessel function, insulin resistance, oxidative stress and faster hardening of the arteries,” said study coauthor Akiva Rosenzveig, M.D., a cardiology fellow at the Cleveland Clinic. “These results indicate GLP1-RAs can help reduce inflammation, improve blood vessel function and manage blood sugar levels.”

The study’s strengths include analyzing a large group of people and examining both death rates and issues related to limbs. For the comparison group, participants had to have received at least 5 metformin prescriptions and no GLP-1 RA prescriptions during the study period. This approach strengthened the analysis results, according to Nanjundappa and colleagues.

“GLP1-RA medications may help people with PAD and Type 2 diabetes live longer. They might also help people reduce the risk of amputation and the number and length of hospitalizations. However, more research is needed to confirm these findings and understand the underlying mechanisms - is it due to reduced inflammation? It would also be important to know if GLP-1 RAs could be beneficial for people with PAD who do not have Type 2 diabetes,” said Joshua J. Joseph, M.D., M.P.H., FAHA, an American Heart Association volunteer expert and chair of the Diabetes Committee for the Association’s Council on Lifestyle and Cardiometabolic Health. Joseph, who was not involved in this study, is an associate professor of internal medicine and the endowed professor for research in internal medicine at The Ohio State University Wexner Medical Center in Columbus, Ohio.

According to the American Heart Association’s 2026 Heart Disease and Stroke Statistics, data from 2021 to 2023 indicate an estimated 29.5 million (10.6%) U.S. adults were diagnosed with Type 2 diabetes. PAD affects about 12.5 million people in the U.S. who are 40 years old or older.

What are the details, background, design and limitations of the study?

• The TriNetX database (global, federated real-world health data network that connects researchers, clinicians and industry partners from over 70–80 healthcare organizations) was used to identify patients ages 18 or older with Type 2 diabetes and PAD from January 2010 through January 2025, and who did not have a new diagnosis of heart attack, end-stage renal disease or stroke within 2 months before receiving a prescription of metformin.
• Researchers compared adults who were prescribed GLP1-RAs at least 5 times during the study period to a comparison group who had no record of GLP1-RA prescriptions throughout the study period. The comparison group had to have had at least 5 prescriptions for metformin.
• The overall PAD group included 3,224 GLP-1 RA users and 6,087 non–GLP-1 RA users; the clogged leg artery subgroup included 750 GLP-1 RA users and 1,616 non–GLP-1 RA users; and the chronic limb-threatening ischemia subgroup included 3,395 GLP-1 RA users and 6,626 non–GLP-1 RA users. After matching, 2,133 patients per group were analyzed in the overall PAD group.
• 63% of participants self-identified as white adults, 23% were Black adults and 45% were women.
• The study was limited in that it could not prove cause and effect. Additionally, electronic health records (digital versions of a patient’s medical record) may have diagnostic coding errors that would impact the results of the analysis.

Co-authors, disclosures and funding sources are listed in the manuscript.

Studies published in the American Heart Association’s scientific journals are peer-reviewed. The statements and conclusions in each manuscript are solely those of the study authors and do not necessarily reflect the Association’s policy or position. The Association makes no representation or guarantee as to their accuracy or reliability. The Association receives more than 85% of its revenue from sources other than corporations. These sources include contributions from individuals, foundations and estates, as well as investment earnings and revenue from the sale of our educational materials. Corporations (including pharmaceutical, device manufacturers and other companies) also make donations to the Association. The Association has strict policies to prevent any donations from influencing its science content and policy positions. Overall financial information is available here.

Additional Resources:

• Multimedia is available on the right column of release link.
• After July 1, view the manuscript online.
• American Heart Association guidelines news release: First-ever clinical guideline issued for cardiovascular-kidney-metabolic (CKM) syndrome (June 2026)
• American Heart Association news release: Healthy lifestyle combined with newer diabetes medications lowered cardiovascular risk (Nov. 2025)
• American Heart Association news release: GLP-1, SGLT2 medications may lower stroke survivor’s risk of future heart attack, stroke (Nov. 2024)
• American Heart Association news release: Medications for Type 2 diabetes, weight loss & kidney health not always provided as needed (March 2024)
• Follow American Heart Association/American Stroke Association news on X @HeartNews
• Follow news from the Journal of the American Heart Association @JAHA_AHA) / X

About the American Heart Association

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